Hydrochloric Acid → HCID 86712671, compound

HRID 1779018Notes

Reaction equation

HRID 1779018 reaction equation
C1C=CC2N(O)N=[N:7]C=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.CCN(C(C)C)C(C)C.[C:33]([O:37][C:38]([N:40]1[CH2:45][CH2:44][CH:43]([C:46]2[CH:51]=[CH:50][C:49]([NH:52][C:53]3[N:58]=[C:57]([CH2:59][CH2:60][C:61]4[CH:66]=[CH:65][CH:64]=[CH:63][C:62]=4[CH2:67][C:68](O)=[O:69])[C:56]([CH3:71])=[CH:55][N:54]=3)=[CH:48][CH:47]=2)[CH2:42][CH2:41]1)=[O:39])([CH3:36])([CH3:35])[CH3:34].C(=O)([O-])[O-].[NH4+].[NH4+]>C1COCC1.CN(C=O)C>[NH2:7][C:68](=[O:69])[CH2:67][C:62]1[CH:63]=[CH:64][CH:65]=[CH:66][C:61]=1[CH2:60][CH2:59][C:57]1[C:56]([CH3:71])=[CH:55][N:54]=[C:53]([NH:52][C:49]2[CH:48]=[CH:47][C:46]([CH:43]3[CH2:42][CH2:41][N:40]([C:38]([O:37][C:33]([CH3:34])([CH3:36])[CH3:35])=[O:39])[CH2:45][CH2:44]3)=[CH:51][CH:50]=2)[N:58]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 517111Ammonium CarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86712670HCID 86712670, compound

Product 1

HCID 86712671HCID 86712671, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

HOBt (49 mg, 0.36 mmol), EDCl.HCl (69 mg, 0.36 mmol) and DIPEA (0.21 mL, 1.2 mmol) were added to a stirred solution of 2-(2-(2-(2-((4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-methylpyrimidin-4-yl)ethyl)phenyl)acetic acid (A55) (127 mg, 0.239 mmol) in dry THF (6 mL) and dry DMF (1 mL) under an atmosphere of nitrogen. After 10 minutes ammonium carbonate (115 mg, 1.20 mmol) was added in one portion and the resulting mixture was stirred at room temperature for 24 hours. The volatiles were removed in vacuo then the residue was partitioned between EtOAc (50 mL) and saturated aqueous NaHCO3 (50 mL). The layers were separated and the aqueous phase was extracted with EtOAc (2×50 mL). The organic extracts were combined, washed with brine and dried over MgSO4. The volatiles were removed under reduced pressure and the residue purified by column chromatography (0-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound A56 as an off-white solid (66 mg, 52%); 1H NMR (400 MHz, d6-DMSO) δ 9.36 (s, 1H), 8.25-8.16 (m, 1H), 7.74 (d, J=8.7 Hz, 2H), 7.49 (s, 1H), 7.28 (m, 1H), 7.25-7.14 (m, 5H), 7.00 (s, 1H), 4.14 (m, 2H), 3.56 (s, 2H), 3.17-3.04 (m, 2H), 2.98-2.91 (m, 2H), 2.84 (m, 2H), 2.71-2.60 (m, 1H), 2.13 (s, 3H), 1.79 (d, J=11.7 Hz, 2H), 1.59-1.43 (m, 11H). LCMS-A: rt 6.078 min; m/z 530 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe residue was partitioned between EtOAc (50 mL) and saturated aqueous NaHCO3 (50 mL)
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with EtOAc (2×50 mL)
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. customThe volatiles were removed under reduced pressure
  8. customthe residue purified by column chromatography (0-100% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-8aa59542cb7c49aea187730edfcd3e99
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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